1) Field of the Invention
Provided is a DNA aptamer selectively binding to the breast cancer-related Her2 (ERBB2) receptor, and a composition for suppressing cancer metastasis or for diagnosing cancer, comprising the same as an active ingredient.
2) Background of the Invention
Breast cancer is the most common cancer in women in advanced countries, such as in the United States and Europe, arising as the primary cause of death among women 40 to 55 years old in the United States. One in 9 women will develop breast cancer at some point during her lifetime. Each year the number of new breast cancer cases increases by 15%. In South Korea, breast cancer accounted for approximately 11.9% of female cancer cases in 1995, and is the third most common cancer in terms of incidence after uterine cervical cancer and stomach cancer. The mortality of breast cancer was reported to come after stomach cancer, hepatic cancer, uterine cancer, and lung cancer in women, and is increasing each year.
Of the total breast cancer cases, approximately 20-25% were observed to have the overexpression of HER-2 protein (ERBB2). It is known that breast cancer with HER-2 overexpression proceeds faster, is more aggressive and responds at a lower yield to Tamoxifen or other particular chemotherapy regimens than that without HER-2 overexpression. Herceptin (Trastuzumab, Genentech), a humanized monoclonal antibody binding to the HER-2 receptor, disrupts the dimerization of the Her-2 receptor to interfere with the signaling of the Her-2 receptor, whereby selective attack against breast cancer cells can be achieved, resulting in a significant increase in the survival of breast cancer patients. Now, herceptin, which selectively targets the Her-2 receptor, has becomes a leading anticancer drug thanks to its sharp increase in sales each year since its launch.
However, herceptin, when administered alone, elicits a response yield as low as approximately 20%, and imparts a very large economic burden to the patient for one year. In addition, this antibody may cause cardiac toxicity in some patients, and herceptin resistance occurs in some patients who have been administered the drug for one year and thus do not respond to herceptin regimens. This is attributed to the fact that herceptin does not act on the exact site for interfering with the dimerization of the Her-2, but on a false site thus resulting in a reduced binding force. Accordingly, many pharmaceutical companies have pursued research and development of alternatives to herceptin, such as Pertuzumab.
In this invention, focus is made on the development of an aptamer which selectively binds to the Her-2 receptor and which overcomes the disadvantages of herceptin, with the expectation that it can be used for the treatment and diagnosis of breast cancer and can effectively remove breast cancer cells when administered in combination with herceptin, thanks to its binding mechanism being different from that of the conventional antibody.